tbuckley/cabot-search huggingface dataset:
Contribution of <scp>MicroRNA</scp>‐27b‐3p to Synovial Fibrotic Responses in Knee Osteoarthritis
Authors: Ghazaleh Tavallaee, Starlee Lively, Jason S. Rockel, Shabana Amanda Ali, Michelle Im, Clementine Sarda, Greniqueca M. Mitchell, Evgeny Rossomacha, Sayaka Nakamura, Pratibha Potla, Sarah Gabrial, John Matelski, Anusha Ratneswaran, Kim Perry, Boris Hinz, Rajiv Gandhi, Igor Jurisica, Mohit Kapoor
Journal: Arthritis & Rheumatology (2022)

Objective Synovial fibrosis contributes to osteoarthritis (OA) pathology, but the underlying mechanisms remain unknown. We have observed increased microRNA‐27b‐3p (miR‐27b‐3p) levels in synovial fluid of patients with late‐stage radiographic knee OA. Here, we investigated the contribution of miR‐27b‐3p to synovial fibrosis in patients with severe knee OA and in a mouse model of knee OA. Methods We stained synovium sections obtained from patients with radiographic knee OA scored according to the Kellgren/Lawrence scale and mice that underwent destabilization of the medial meniscus (DMM) for miR‐27b‐3p using in situ hybridization. We examined the effects of intraarticular injection of miR‐27b‐3p mimic into naive mouse knee joints and intraarticular injection of a miR‐27b‐3p inhibitor into mouse knee joints after DMM. We performed transfection with miR‐27b‐3p mimic and miR‐27b‐3p inhibitor in human OA fibroblast‐like synoviocytes (FLS) using reverse transcriptase–quantitative polymerase chain reaction (RT‐qPCR) array, RNA sequencing, RT‐qPCR, Western blotting, immunofluorescence, and migration assays. Results We observed increased miR‐27b‐3p expression in the synovium from patients with knee OA and in mice with DMM‐induced arthritis. Injection of the miR‐27b‐3p mimic in mouse knee joints induced a synovial fibrosis‐like phenotype, increased synovitis scores, and increased COL1A1 and α‐smooth muscle actin (α‐SMA) expression. In the mouse model of DMM‐induced arthritis, injection of the miR‐27b‐3p inhibitor decreased α‐SMA but did not change COL1A1 expression levels or synovitis scores. Transfection with the miR‐27b‐3p mimic in human OA FLS induced profibrotic responses, including increased migration and expression of key extracellular matrix (ECM) genes, but transfection with the miR‐27b‐3p inhibitor had the opposite effects. RNA sequencing identified a PPARG/ADAMTS8 signaling axis regulated by miR‐27b‐3p in OA FLS. Human OA FLS transfected with miR‐27b‐3p mimic and then treated with the PPARG agonist rosiglitazone or with ADAMTS8 small interfering RNA exhibited altered expression of select ECM genes. Conclusion Our findings demonstrate that miR‐27b‐3p has a key role in ECM regulation associated with synovial fibrosis during OA.
Decoding Shared Versus Divergent Transcriptomic Signatures Across Cortico-Amygdala Circuitry in PTSD and Depressive Disorders
Authors: Andrew E. Jaffe, Ran Tao, Stephanie C. Page, Kristen R. Maynard, Elizabeth A. Pattie, Claudia V. Nguyen, Amy Deep-Soboslay, Rahul Bharadwaj, Keith A. Young, Matthew J. Friedman, Douglas E. Williamson, Joo Heon Shin, Thomas M. Hyde, Keri Martinowich, Joel E. Kleinman
Journal: American Journal of Psychiatry (2022)

Objective: Posttraumatic stress disorder (PTSD) is a debilitating neuropsychiatric disease that is highly comorbid with major depressive disorder (MDD) and bipolar disorder. The overlap in symptoms is hypothesized to stem from partially shared genetics and underlying neurobiological mechanisms. To delineate conservation between transcriptional patterns across PTSD and MDD, the authors examined gene expression in the human cortex and amygdala in these disorders. Methods: RNA sequencing was performed in the postmortem brain of two prefrontal cortex regions and two amygdala regions from donors diagnosed with PTSD (N=107) or MDD (N=109) as well as from neurotypical donors (N=109). Results: The authors identified a limited number of differentially expressed genes (DEGs) specific to PTSD, with nearly all mapping to cortical versus amygdala regions. PTSD-specific DEGs were enriched in gene sets associated with downregulated immune-related pathways and microglia as well as with subpopulations of GABAergic inhibitory neurons. While a greater number of DEGs associated with MDD were identified, most overlapped with PTSD, and only a few were MDD specific. The authors used weighted gene coexpression network analysis as an orthogonal approach to confirm the observed cellular and molecular associations. Conclusions: These findings provide supporting evidence for involvement of decreased immune signaling and neuroinflammation in MDD and PTSD pathophysiology, and extend evidence that GABAergic neurons have functional significance in PTSD.
Relevance of Bone Marrow Biopsies for Response Assessment in US National Cancer Institute National Clinical Trials Network Follicular Lymphoma Clinical Trials
Authors: Sarah C. Rutherford, Jun Yin, Levi Pederson, Gabriela Perez Burbano, Betsy LaPlant, Mazyar Shadman, Hongli Li, Michael L. LeBlanc, Vaishalee P. Kenkre, Fangxin Hong, Kristie A. Blum, Travis Dockter, Peter Martin, Sin-Ho Jung, Barbara Grant, Cara Rosenbaum, Chaitra Ujjani, Paul M. Barr, Joseph M. Unger, Bruce D. Cheson, Nancy L. Bartlett, Brad Kahl, Jonathan W. Friedberg, Sumithra J. Mandrekar, John P. Leonard
Journal: Journal of Clinical Oncology (2022)

Bone marrow biopsies (BMB) are performed before/after therapy to confirm complete response (CR) in patients with lymphoma on clinical trials. We sought to establish whether BMB add value in assessing response or predict progression-free survival (PFS) or overall survival (OS) outcomes in follicular lymphoma (FL) subjects in a large, multicenter, multitrial cohort.
Expiration Dates Extended on COVID-19 Monoclonal Antibody Therapies
Authors: Howard D. Larkin
Journal: JAMA (2022)

Expiration dates on several monoclonal antibody therapies for COVID-19 were extended by the FDA and the US Department of Health and Human Services’ Assistant Secretary for Preparedness and Response (ASPR) as a way to preserve supplies of the drugs for future outbreaks.
Modulation of the Itaconate Pathway Attenuates Murine Lupus
Authors: Luz P. Blanco, Eduardo Patino‐Martinez, Shuichiro Nakabo, Mingzeng Zhang, Hege L. Pedersen, Xinghao Wang, Carmelo Carmona‐Rivera, Dillon Claybaugh, Zu‐Xi Yu, Equar Desta, Mariana J. Kaplan
Journal: Arthritis & Rheumatology (2022)

Itaconic acid, a Krebs cycle-derived immunometabolite, is synthesized by myeloid cells in response to danger signals to control inflammasome activation, type I interferon (IFN) responses, and oxidative stress. As these pathways are dysregulated in systemic lupus erythematosus (SLE), we investigated the role of an itaconic acid derivative in the treatment of established murine lupus.
Lu3+-based nanoprobe for virtual non-contrast CT imaging of hepatocellular carcinoma
Authors: Jiayao Chen, Jiani Liu, Duo Xu, Junfeng Liu, Xiaojun Chen, Shuai Yang, Pan Yin, Zebo Jiang, Chaoming Mei, Xiaoting Zhang, Lizhu Wang, Ke Zhang, Bin Zhou, Hong Shan, Dan Li, Pengfei Pang
Journal: Journal of Controlled Release (2022)
Combining lipid based drug delivery and amorphous solid dispersions for improved oral drug absorption of a poorly water-soluble drug
Authors: Georgia-Ioanna Nora, Ramakrishnan Venkatasubramanian, Sophie Strindberg, Scheyla Daniela Siqueira-Jørgensen, Livia Pagano, Francis S. Romanski, Nitin K. Swarnakar, Thomas Rades, Anette Müllertz
Journal: Journal of Controlled Release (2022)

Two widely applied enabling drug delivery approaches, self-nanoemulsifying drug delivery systems (SNEDDS) and amorphous solid dispersions (ASD), were combined, with the aim of enhancing physical stability, solubilization and absorption of the model drug ritonavir. Ritonavir was loaded at a concentration above its saturation solubility (Seq) in the SNEDDS (superSNEDDS, 250% of Seq). An ASD of ritonavir with polyvinylpyrrolidone-vinyl acetate copolymers (Kollidon® VA64) was prepared by ball milling. Relevant control formulations, which include conventional SNEDDS (90% of Seq), superSNEDDS with a physical mix of Kollidon® VA64 and ritonavir (superSNEDDS+PM) and an aqueous suspension of ritonavir were used. A pharmacokinetic (PK) study in rats was performed to assess the relative bioavailability of ritonavir after oral administration. This was followed by evaluating the formulations in a novel two-step in vitro lipolysis model simulating rat gastric and intestinal conditions. The addition of a ritonavir containing ASD to superSNEDDS increased the degree of supersaturation from 250% to 275% Seq in the superSNEDDS and the physical stability (absence of drug recrystallization) of the system from 48 h to 1 month under ambient conditions. The PK study in rats displayed significantly higher Cmax and AUC0-7h (3-fold increase) and faster Tmax for superSNEDDS+ASD compared to the conventional SNEDDS whilst containing 3 times less lipid than the latter. Furthermore, superSNEDDS+ASD were able to keep the drug solubilised during in vitro lipolysis to the same degree as the conventional SNEDDS. These findings suggest that dissolving an ASD in a superSNEDDS can contribute to the development of novel oral delivery systems with increased bioavailability for poorly water-soluble drugs.
Prostate Cancer Screening at US Cancer Centers—Reply
Authors: Jennifer L. Marti, Andrew Y. J. Lee, Elizabeth S. Koh
Journal: JAMA Internal Medicine (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
A Review of the Diagnosis and Treatment of Pulmonary Sarcoidosis—Reply
Authors: John A. Belperio, S. Samuel Weigt, Joseph P. Lynch
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Physiological Murmur in a Pregnant Woman
Authors: Anamika Karn, Shital Khanal, Abhishek Thakur
Journal: JAMA Internal Medicine (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2022 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Comparison of Pregnancy Preferences Preceding vs Year 1 of the COVID-19 Pandemic
Authors: Corinne H. Rocca, Miriam Parra, Isabel Muñoz, Diana G. Foster, W. John Boscardin, Lauren J. Ralph
Journal: JAMA Network Open (2022)

Understanding how the COVID-19 pandemic affected people's desire to avoid pregnancy is essential for interpreting the pandemic's associations with access to reproductive health care and reproductive autonomy. Early research is largely cross-sectional and relies on people's own evaluations of how their desires changed.
Spending and Out-of-Pocket Costs for Genital Gender-Affirming Surgery in the US
Authors: Jae Downing, Sarah K. Holt, Michael Cunetta, John L. Gore, Geolani W. Dy
Journal: JAMA Surgery (2022)

Genital gender-affirming surgery (GAS) is safe and offers substantial benefits to patients. Geographic accessibility and high out-of-pocket (OOP) costs reportedly hinder access; however, to date, this has not been thoroughly investigated at the national level.
Drug Interactions With Nirmatrelvir-Ritonavir in Older Adults Using Multiple Medications
Authors: Sydney B. Ross, Émilie Bortolussi-Courval, Ryan Hanula, Todd Campbell Lee, Marnie Goodwin Wilson, Emily G. McDonald
Journal: JAMA Network Open (2022)

This quality improvement study uses data from the MedSafer trial to evaluate drug-drug interactions between nirmatrelvir-ritonavir and maintenance medications to identify use of potentially inappropriate medications in older adults with polypharmacy.
Cytokine‐ and chemokine‐induced inflammatory colorectal tumor microenvironment: Emerging avenue for targeted therapy
Authors: Ajaz A. Bhat, Sabah Nisar, Mayank Singh, Bazella Ashraf, Tariq Masoodi, Chandra P. Prasad, Atul Sharma, Selma Maacha, Thasni Karedath, Sheema Hashem, Syed Besina Yasin, Puneet Bagga, Ravinder Reddy, Michael P. Frennaux, Shahab Uddin, Punita Dhawan, Mohammad Haris, Muzafar A. Macha
Journal: Cancer Communications (2022)

Abstract Colorectal cancer (CRC) is a predominant life‐threatening cancer, with liver and peritoneal metastases as the primary causes of death. Intestinal inflammation, a known CRC risk factor, nurtures a local inflammatory environment enriched with tumor cells, endothelial cells, immune cells, cancer‐associated fibroblasts, immunosuppressive cells, and secretory growth factors. The complex interactions of aberrantly expressed cytokines, chemokines, growth factors, and matrix‐remodeling enzymes promote CRC pathogenesis and evoke systemic responses that affect disease outcomes. Mounting evidence suggests that these cytokines and chemokines play a role in the progression of CRC through immunosuppression and modulation of the tumor microenvironment, which is partly achieved by the recruitment of immunosuppressive cells. These cells impart features such as cancer stem cell‐like properties, drug resistance, invasion, and formation of the premetastatic niche in distant organs, promoting metastasis and aggressive CRC growth. A deeper understanding of the cytokine‐ and chemokine‐mediated signaling networks that link tumor progression and metastasis will provide insights into the mechanistic details of disease aggressiveness and facilitate the development of novel therapeutics for CRC. Here, we summarized the current knowledge of cytokine‐ and chemokine‐mediated crosstalk in the inflammatory tumor microenvironment, which drives immunosuppression, resistance to therapeutics, and metastasis during CRC progression. We also outlined the potential of this crosstalk as a novel therapeutic target for CRC. The major cytokine/chemokine pathways involved in cancer immunotherapy are also discussed in this review.
Dutch Physician’s Perspectives on Diagnosis and Treatment of Waldenström’s Macroglobulinemia Before and After the Implementation of a National Guideline
Authors: Karima Amaador, Marie José Kersten, Monique C. Minnema, Josephine M. I. Vos
Journal: HemaSphere (2022)

Waldenström's macroglobulinemia (WM), a rare low-grade B-cell non-Hodgkin lymphoma (NHL), has a distinct clinical presentation and different treatment-related side effects compared with other NHL. Currently, a wide variety of therapeutic agents are available for the treatment of WM but there is no consensus on optimal treatment in first line and/or at relapse. The aim of this survey was to evaluate the current knowledge and perspectives of hematologists on diagnosis and treatment of WM. Also, we compare these results to a similar survey done before the publication of the first Dutch national guideline, in order to evaluate the impact of the implementation of a national guideline. A link to an online survey was sent out to all registered hematologists and hemato-oncologists in the Netherlands with the request to participate. The survey contained questions regarding the preferred diagnostic and treatment methods in patients with WM as well as treatment goals. We also compared physicians preferred treatment goals to those of patients (as studied in a recent nationwide patient questionnaire). Ninety-five responses (30% response rate) were obtained, out of which 82 (86%) surveys were complete. The respondents most commonly used dexamethasone-rituximab-cyclophosphamide as first-line treatment. For second-line treatment, bendamustine with rituximab and ibrutinib monotherapy were the most frequently applied. Compared with the initial survey, serum IgM M-protein was determined in all cases, MYD88 mutation analysis was currently widely implemented, prevention of an IgM "flare" was uniformly managed by the respondents and use of rituximab-cyclophosphamide-vincristine-prednisone was entirely abandoned. Physicians differed somewhat from patients with regard to most important treatment goals. The approach to diagnostic methods and treatment options in WM was more consistent with international guidelines and was more homogeneous after implementation of the national guideline. These data indicate an increase in knowledge on WM diagnosis and treatment. This may have resulted from implementation of a local guideline or the global rise in awareness and attention for WM.
Detection of Brain Tau Pathology in Down Syndrome Using Plasma Biomarkers
Authors: Shorena Janelidze, Bradley T. Christian, Julie Price, Charles Laymon, Nicole Schupf, William E. Klunk, Ira Lott, Wayne Silverman, H. Diana Rosas, Shahid Zaman, Mark Mapstone, Florence Lai, Beau M. Ances, Benjamin L. Handen, Oskar Hansson
Journal: JAMA Neurology (2022)

Novel plasma biomarkers, especially phosphorylated tau (p-tau), can detect brain tau aggregates in Alzheimer disease.
Brief exposure to directionally-specific pulsed electromagnetic fields stimulates extracellular vesicle release and is antagonized by streptomycin: A potential regenerative medicine and food industry paradigm
Authors: Craig Jun Kit Wong, Yee Kit Tai, Jasmine Lye Yee Yap, Charlene Hui Hua Fong, Larry Sai Weng Loo, Marek Kukumberg, Jürg Fröhlich, Sitong Zhang, Jing Ze Li, Jiong-Wei Wang, Abdul Jalil Rufaihah, Alfredo Franco-Obregón
Journal: Biomaterials (2022)

Pulsing electromagnetic fields (PEMFs) have been shown to promote in vitro and in vivo myogeneses via mitohormetic survival adaptations of which secretome activation is a key component. A single 10-min exposure of donor myoblast cultures to 1.5 mT amplitude PEMFs produced a conditioned media (pCM) capable of enhancing the myogenesis of recipient cultures to a similar degree as direct magnetic exposure. Downwardly-directed magnetic fields produced greater secretome responses than upwardly-directed fields in adherent and fluid-suspended myoblasts. The suspension paradigm allowed for the rapid concentrating of secreted factors, particularly of extracellular vesicles. The brief conditioning of basal media from magnetically-stimulated myoblasts was capable of conferring myoblast survival to a greater degree than basal media supplemented with fetal bovine serum (5%). Downward-directed magnetic fields, applied directly to cells or in the form of pCM, upregulated the protein expression of TRPC channels, markers for cell cycle progression and myogenesis. Direct magnetic exposure produced mild oxidative stress, whereas pCM provision did not, providing a survival advantage on recipient cells. Streptomycin, a TRP channel antagonist, precluded the production of a myogenic pCM. We present a methodology employing a brief and non-invasive PEMF-exposure paradigm to effectively stimulate secretome production and release for commercial or clinical exploitation.
Long noncoding RNA Smyca coactivates TGF-β/Smad and Myc pathways to drive tumor progression
Authors: Hsin-Yi Chen, Shu-Jou Chan, Xinxin Liu, An-Chi Wei, Ru-In Jian, Kuan-Wei Huang, Yaw-Dong Lang, Jou-Ho Shih, Chun-Chieh Liao, Chiu-Lin Luan, Yu-Tung Kao, Shang-Yin Chiang, Pei-Wen Hsiao, Yuh-Shan Jou, Yunching Chen, Ruey-Hwa Chen
Journal: Journal of Hematology & Oncology (2022)

Abstract Background Metastasis and chemoresistance are major culprits of cancer mortality, but factors contributing to these processes are incompletely understood. Methods Bioinformatics methods were used to identify the relations of Smyca expression to clinicopathological features of human cancers. RNA-sequencing analysis was used to reveal Smyca -regulated transcriptome. RNA pull-down and RNA immunoprecipitation were used to examine the binding of Smyca to Smad3/4 and c-Myc/Max. Chromatin immunoprecipitation and chromatin isolation by RNA purification were used to determine the binding of transcription factors and Smyca to various gene loci, respectively. Real-time RT-PCR and luciferase assay were used to examine gene expression levels and promoter activities, respectively. Xenograft mouse models were performed to evaluate the effects of Smyca on metastasis and chemoresistance. Nanoparticle-assisted gapmer antisense oligonucleotides delivery was used to target Smyca in vivo. Results We identify lncRNA Smyca for its association with poor prognosis of many cancer types. Smyca potentiates metabolic reprogramming, migration, invasion, cancer stemness, metastasis and chemoresistance. Mechanistically, Smyca enhances TGF-β/Smad signaling by acting as a scaffold for promoting Smad3/Smad4 association and further serves as a Smad target to amplify/prolong TGF-β signaling. Additionally, Smyca potentiates c-Myc-mediated transcription by enhancing the recruitment of c-Myc/Max complex to a set of target promoters and c-Myc binding to TRRAP. Through potentiating TGF-β and c-Myc pathways, Smyca synergizes the Warburg effect elicited by both pathways but evades the anti-proliferative effect of TGF-β. Targeting Smyca prevents metastasis and overcomes chemoresistance. Conclusions This study uncovers a lncRNA that coordinates tumor-relevant pathways to orchestra a pro-tumor program and establishes the clinical values of Smyca in cancer prognosis and therapy.